Novel respiratory syncytial virus replication inhibitors based on monoterpene conjugates and 3-substituted 7-hydroxycoumarins

Respiratory syncytial virus (RSV) causes respiratory infections, leading to annual epidemics in the cold seasons. It is especially dangerous for infants and the elderly. 

Coumarin and its derivatives have a wide range of pharmacological properties, including antitumor, antibacterial and antiviral activity, as well as anti-HIV, anti-inflammatory and anticoagulant properties.

Significant progress in recent decades has been made in identifying potential targets for RSV therapy and in the search for small molecule inhibitors of RSV replication. Thus, 7-hydroxycoumarins monoterpene conjugates containing various substituents at С-4 position of the coumarin scaffold proved to be effective. Later it was suggested that the use of their analogues with substituents at C-3 position of the coumarin backbone may be promising for RSV replication inhibition, based on molecular docking to RSV protein F as molecular target which is responsible for virus entry into the host cell [1]. 

In this work we synthesized the first eighteen conjugates of C-3 substituted 7-hydroxycoumarins, thus developed and optimized methods for the synthesis of these compounds. Among the synthesized compounds, agents demonstrating promising anti-RSV activity with IC₅₀ in the lower micromolar range were found. The compounds are most active in the early stages of infection, apparently preventing the virus from entering the cell by binding to the F RSV protein.
1. Khomenko, T. M.; Shtro, A. A.; Galochkina, A. v.; Nikolaeva, Y. v.; Garshinina, A. v.; Borisevich, S. S.; Korchagina, D. v.; Volcho, K. P.; Salakhutdinov, N. F. New Inhibitors of Respiratory Syncytial Virus (RSV) Replication Based on Monoterpene-Substituted Arylcoumarins. Molecules 2023, 28 (6), 2673. https://doi.org/10.3390/molecules28062673.